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US 10,329,298 B2Granted
Inhibitors of cellular metabolic processes
AssigneeAgios Pharmaceuticals, Inc.
InventorsZenon D. Konteatis, Zhihua Sui, Jeremy M. Travins, Zhixiong Ye
Life of this patent
Estimating the term…
Abstract
The present disclosure provides MAT2A inhibitor compounds that are useful as therapeutic agents for treating malignancies, and wherein the compounds conform to general formula (IA): wherein RA, RB, RC, RD, and RE are defined herein.
Claims32
A compound according to formula IA or a pharmaceutically acceptable salt thereof:
- wherein
- RA is selected from the group consisting of H, C1-C6-alkyl, C2-C6-alkenyl, C1-C6-alkoxy, C3-C14-carbocycle, (C3-C14-carbocyclo)-C1-C6-alkyl-, 3- to 14-membered heterocycle or heterocyclo-C1-C6-alkyl- (wherein 1 to 4 heterocycle ring members are heteroatoms selected from N, O, and S), (3- to 14-membered heterocyclo)oxy-, C6-C14-aryl, (C6-C14-aryl)-C1-C6-alkyl-, C6-C14-aryloxy-, —(CH2)0-6NR1(CH2)0-6C(O)R2, NR1R2, C(O)NR1R2, NR1C(NR2)NR1R2, NR1C(NR2)(═NR1), SR1, —CN, and —OH;
- wherein each alkyl, alkenyl, alkoxy, aryl, and heterocycle is optionally substituted with one or more substituents selected from the group consisting of R, OR1, halo, —N═N—R1, NR1R2, —(C1-C6-alkyl)NR1R2, —C(O)OR1, —C(O)NR1R2, —OC(O)R1, —CN, —OP(O)(OR1)1-2, and oxo;
- RB is selected from the group consisting of H, C2-C6-alkenyl, and C1-C6-alkyl, wherein RB is optionally substituted by one or more R1;
- RC, RD, and RE are independently selected from the group consisting of C3-C14-carbocycle, C6-C14-aryl, and 3- to 14-membered heterocycle (wherein 1 to 4 heterocycle ring members are heteroatoms selected from N, O, and S),
- wherein RC, RD, and RE are optionally substituted with one or more substituents selected from the group consisting of R1, —OR1, halo, —NR1R2, —(C1-C6-alkyl)-NR1R2, —C(O)OR1, —C(O)NR1R2, —NO2, —CN, and oxo;
- and
- R1 and R2 are independently selected from the group consisting of H, D (2H), —CN, —OH, C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, NH2, —S(O)0-2—(C1-C6-alkyl), —S(O)0-2-(C6-C14-aryl), —C(O)(C1-C6-alkyl), —C(O)(C3-C14-carbocyclo), —C3-C14-carbocycle, C6-C14-aryl, 3- to 14-membered heterocycle or heterocyclo(C1-C6-alkyl)- (wherein 1 to 4 heterocycle ring members are heteroatoms selected from N, O, and S),
- wherein each alkyl, alkoxy, alkenyl, alkynyl, aryl, carbocycle, and heterocycle moiety of R1 and R2 is optionally substituted with one or more substituents selected from the group consisting of hydroxy, halo, —NH2, —NHC(O)(OC1-C6-alkyl), —NO2, —CN, oxo, —C(O)OH, —C(O)O(C1-C6-alkyl), —C1-C6-alkyl(C1-C6-alkoxy), —C(O)NH2, C1-C6-alkyl, —C(O)C1-C6-alkyl, —OC1-C6-alkyl, —Si(C1-C6-alkyl)3, C6-C14-aryl, —(C1-C6-alkyl)(C6-C14-aryl), 3- to 14-membered heterocycle or heterocyclo(C1-C6-alkyl)- (wherein 1 to 4 heterocycle ring members are heteroatoms selected from N, O, and S), and —O(C6-C14-aryl),
- wherein each alkyl, aryl, and heterocyclo in R1 and R2 is optionally substituted with one or more substituents selected from the group consisting of hydroxy, —OC1-C6-alkyl, halo, —NH2, —(C1-C6-alkyl)NH2, —C(O)OH, CN, and oxo.
7 more elements
A compound of formula (I) or a pharmaceutically acceptable salt thereof:
- wherein:
- ring A and ring B are independently a carbocycle or a heterocycle each optionally substituted with one or more substituents selected from the group consisting of hydroxy, halogen, amino, carboxy, CN, oxo, alkyl, alkoxy and alkylamino wherein said alkyl, alkoxy and alkylamino are optionally substituted with hydroxy, halogen, amino, carboxy, CN and oxo;
- ring C is a carbocycle or a heterocycle each optionally substituted with one or more substituents selected from the group consisting of hydroxy, halogen, amino, carboxy, CN, oxo, alkyl, alkoxy and alkylamino wherein said alkyl, alkoxy and alkylamino are optionally substituted with hydroxy, halogen, amino, carboxy, CN and oxo;
- and
- R1 is H or alkyl, a carbocycle or a heterocycle each optionally substituted with one or more substituents selected from the group consisting of hydroxy, halogen, amino, NO2, CN, oxo, carboxy, alkoxycarbonyl, alkoxyalkyl, aminocarbonyl, alkyl, acyl, alkoxy, alkylamino aryl, aralkyl, heteroaryl, heteroaralkyl, aryloxy, aralkoxy, heteroaryloxy and heteroaralkoxy wherein said alkyl, alkoxy, alkylamino, alkoxycarbonyl, alkoxyalkyl, aminocarbonyl, aryl, aralkyl, heteroaryl, heteroaralkyl, aryloxy, aralkoxy, heteroaryloxy and heteroaralkoxy are optionally substituted with hydroxy, halogen, amino, alkylamino, carboxy, CN or oxo.
2 more elements
Dependencies are inferred from the claim text.